Esterase Inhibition in SH-SY5Y Human Neuroblastoma Cells Following Exposure to Organophosphorus Compounds for 28 Days

Abstract

Esterase inhibition was determined in SH-SY5Y human neuroblastoma cells grown in serum-free media and exposed to 10^-11 to 10^-7 M concentrations of organophosphorus (OP) compounds for 28 days. To examine metabolic activation in these exposures, pairs of pro- and active toxicants were studied, including chlorpyrifos and its oxon, parathion and paraoxon, and tri-ortho-tolyl phosphate and phenyl saligenin phospahte. Inhibition of acetylcholinesterase was greater in cells treated for 28 days with all active organophosphorus compounds than it was in cells treated only once with the same concentration of a given OP compound. The protoxicants chlorpyrifos and parathion produced acetylcholinesterase inhibition after multiple exposures although no inhibition was seen following a single exposure to these agents. Exacerbation of neurotoxic esterase inhibition by multiple exposures to the test compounds was not as pronounced as that of acetylcholinesterase. Exposure to the test compounds for 28 days did not significantly enhance esterase inhibition produced by a subsequent exposure to 10^-9 M chlorpyrifos-oxon. The results indicate that in vitro methods can be used to study the effect of multiple OP exposures on esterase activity.